Method for synthesizing benzyl sulfoxide through selective oxidation of thioanisole

Abstract

The invention relates to a method for synthesizing benzyl sulfoxide through selective oxidation of benzyl sulfide, belongs to the technical field of fine organic synthesis, and can overcome the defects of complex synthesis process steps, complex catalyst preparation, long reaction time and the like in the existing benzyl sulfoxide synthesis. Meanwhile, tert-butyl alcohol is introduced as an inhibitor to regulate and control the reaction process, ethyl acetate is used as a reaction solvent, and benzyl sulfoxide is prepared through selective oxidation. The innovative process has the advantages of mild process conditions, environmental friendliness, no need of adding any catalyst, high product yield and the like. The method shows huge potential and value in the field of industrial application.

Description

Technical Field

[0001] The invention belongs to the technical field of fine organic synthesis, and particularly relates to a method for synthesizing benzyl sulfoxide by selective oxidation of thioanisole. Background Art

[0002] Compounds containing sulfoxide structural units are important intermediates in organic synthesis, with broad-spectrum biological activity and wide application value. One of the main methods for preparing sulfoxides is the selective oxidation of thioethers. Commonly used oxidants for this oxidation reaction include metal oxides, inorganic and organic oxidants, etc. These oxidants have disadvantages to varying degrees. For example, some oxidants produce an equal amount of low-valent reduction products during the reaction, which not only increases the difficulty of product separation and purification, but also has adverse effects on the environment when these wastes are treated. Ozone, as an oxidant without secondary pollution, has the advantages of simple post-reaction treatment and water as a by-product. The expansion of this method has received special attention from chemists.

[0003] Patent 201610533582.9 discloses a method for synthesizing a caged compound and its application. The caged compound is a Schiff base compound obtained by condensing a "bidentate" Ni(II)Salen-(R1-R1) ligand with an amine compound through an amine aldehyde. The caged compound prepared by the present invention can catalyze the selective oxidation of anisole and the like to synthesize corresponding sulfoxide compounds with high activity and high selectivity. Patent 201710008667.X discloses a porous organic polymer skeleton material and its preparation method and application. The method uses 2,7-di-(nitrogen-carbazolyl)-9-oxone as a structural unit, uses dimethanol formal as a cross-linking agent, and obtains a porous organic polymer skeleton material connected by methylene under the catalysis of a Lewis acid catalyst. The porous organic polymer skeleton material can be used for photocatalytic organic amine selective synthesis of imine or photocatalytic sulfide selective synthesis of sulfoxide. Although the present invention has a good reaction effect, the catalyst preparation process is cumbersome and separation and reuse are difficult. Patent 201910565960.5 The present invention discloses a method for synthesizing sulfoxide compounds, which belongs to the technical field of organic compound synthesis. The method of the present invention uses perylene imide as a catalyst to catalyze the reaction of sulfide compounds with oxygen agents under light conditions to obtain sulfoxide compounds. The present invention realizes the synthesis of sulfoxides by catalytic oxidation of sulfide by perylene imide. The method can only be carried out under light conditions, and the catalyst structure is relatively complex, and its preparation process is complicated.

[0004] The current synthesis of benzyl sulfoxide has the disadvantages of cumbersome synthesis process steps, complex catalyst preparation, long reaction time, etc. Therefore, it is of great industrial application value to develop a new method for synthesizing benzyl sulfoxide with mild process conditions, simple operation, high efficiency and environmental protection, no catalyst and wide applicability. Summary of the invention

[0005] The invention aims at the disadvantages of the current synthesis of benzyl sulfoxide, such as cumbersome synthesis process steps, complicated catalyst preparation, long reaction time, etc., and provides a method for synthesizing benzyl sulfoxide by selective oxidation of anisyl thioether.

[0006] The present invention adopts the following technical solution: A method for synthesizing benzyl sulfoxide by selective oxidation of thioanisole comprises the following steps: In the first step, thioanisole, tert-butyl alcohol and ethyl acetate are added into the reaction bottle in sequence; The second step is to adjust the pressure reducing valve of the oxygen cylinder and set the partial pressure to 0.1 MPa. After the oxygen enters the ozone generator, an ozone mixed gas is generated. The gas flow rate is set to 100 L / h. The ozone mixed gas enters the reaction bottle to react with the reactants. The gas phase concentration of ozone is controlled to be 20-100 mg / L. The third step is to introduce the ozone mixed gas into the reaction bottle, and set the reaction liquid temperature to 25°C and the reaction time to 30-60 minutes; The fourth step is to remove the reaction solvent by distillation under reduced pressure after the reaction is completed, and then separate the product benzyl sulfoxide by column chromatography.

[0007] Furthermore, the dosage of thioanisole in the first step is 1-5 mL.

[0008] Furthermore, the amount of tert-butyl alcohol used in the first step is 100-500 mg.

[0009] Furthermore, in the first step, the volume ratio of thioanisole to ethyl acetate is 1:50 to 1:100.

[0010] The beneficial effects of the present invention are as follows: The invention uses anisyl thioether as a reactant, ozone as an oxidant, and tert-butyl alcohol as an inhibitor, and does not need to add any catalyst. Under normal pressure, anisyl thioether is selectively oxidized to prepare anisyl sulfoxide, and the method has the characteristics of mild process conditions, simple operation, high efficiency, environmental protection, no catalyst, and wide applicability. The specific reaction process is that ozone first attacks the sulfur atom in anisyl thioether, and then decomposes anisyl mercaptan with strong activity, and ozone and anisyl mercaptan undergo 1,3-dipole insertion reaction to decompose and generate anisyl sulfoxide and other active free radicals, which are quenched by tert-butyl alcohol, thereby reducing the reaction process of deep oxidation of anisyl sulfoxide to anisyl sulfone, thereby improving the selectivity of anisyl sulfoxide. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 is the equation for synthesizing benzyl sulfoxide by selective oxidation of thioanisole by ozone oxidation of the present invention; Figure 2 The target product of the present invention1 H NMR spectrum; Figure 3 The target product of the present invention 13 C NMR spectrum. DETAILED DESCRIPTION

[0012] The technical solution of the present invention will be clearly and completely described below in combination with the embodiments of the present invention and the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0013] Example 1 Weigh 1 mL of thioanisole, 100 mL of ethyl acetate, and 200 mg of tert-butanol, and place them in a reaction bottle. Adjust the pressure reducing valve of the oxygen cylinder and set the partial pressure to 0.1 MPa. After the oxygen enters the ozone generator, an ozone mixed gas is generated. Set the gas flow rate to 100 L / h and the gas phase concentration of ozone to 50 mg / L. After reacting for 30 minutes at a reaction temperature of 25°C, remove the reaction solvent by reduced pressure distillation, and then separate by column chromatography to obtain the product phenylmethyl sulfoxide with a yield of 65%.

[0014] 1 H NMR (400 MHz, CDCl3) δ7.67-7.63 (m, 2H), 7.54-7.46 (m, 3H), 2.71 (s, 3H).

[0015] 13 C NMR (100 MHz, CDCl3) δ 145.69, 130.97, 129.30, 123.42, 43.90.

[0016] Example 2 Weigh 5 mL of thioanisole, 250 mL of ethyl acetate, and 500 mg of tert-butanol, and place them in a reaction flask. Adjust the pressure reducing valve of the oxygen cylinder and set the partial pressure to 0.1 MPa. After the oxygen enters the ozone generator, an ozone mixed gas is generated. The gas flow rate is set to 100 L / h, and the gas phase concentration of ozone is 100 mg / L. After reacting for 60 minutes at a reaction temperature of 25°C, the reaction solvent is removed by reduced pressure distillation, and the product phenylmethyl sulfoxide is separated by column chromatography to obtain phenylmethyl sulfoxide with a yield of 78%.

[0017] 1H NMR (400 MHz, CDCl3) δ 7.67-7.63 (m, 2H), 7.54-7.46 (m, 3H), 2.71 (s, 3H).

[0018] 13 C NMR (100 MHz, CDCl3) δ 145.69, 130.97, 129.30, 123.42, 43.90.

[0019] Example 3 Weigh 2 mL of thioanisole, 200 mL of ethyl acetate and 100 mg of tert-butanol, and place them in a reaction flask. Adjust the pressure reducing valve of the oxygen cylinder and set the partial pressure to 0.1 MPa. After the oxygen enters the ozone generator, an ozone mixed gas is generated. The gas flow rate is set to 100 L / h and the gas phase concentration of ozone is 60 mg / L. After reacting for 45 minutes at a reaction temperature of 25°C, the reaction solvent is removed by reduced pressure distillation and the product phenylmethyl sulfoxide is separated by column chromatography to obtain phenylmethyl sulfoxide in a yield of 68%.

[0020] 1 H NMR (400 MHz, CDCl3) δ 7.67-7.63 (m, 2H), 7.54-7.46 (m, 3H), 2.71 (s, 3H).

[0021] 13 C NMR (100 MHz, CDCl3) δ 145.69, 130.97, 129.30, 123.42, 43.90.

[0022] Example 4 Weigh 3 mL of thioanisole, 150 mL of ethyl acetate, and 200 mg of tert-butanol, and place them in a reaction flask. Adjust the pressure reducing valve of the oxygen cylinder and set the partial pressure to 0.1 MPa. After the oxygen enters the ozone generator, an ozone mixed gas is generated. The gas flow rate is set to 100 L / h and the gas phase concentration of ozone is 80 mg / L. After reacting for 60 minutes at a reaction temperature of 25°C, the reaction solvent is removed by reduced pressure distillation and the product phenylmethyl sulfoxide is separated by column chromatography to obtain phenylmethyl sulfoxide in a yield of 72%.

[0023] 1 H NMR (400 MHz, CDCl3) δ 7.67-7.63 (m, 2H), 7.54-7.46 (m, 3H), 2.71 (s, 3H).

[0024] 13 C NMR (100 MHz, CDCl3) δ 145.69, 130.97, 129.30, 123.42, 43.90.

[0025] Only the preferred embodiments of the present invention are described in detail above, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge scope of ordinary technicians in this field without departing from the purpose of the present invention, and various changes should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing benzyl sulfoxide by selective oxidation of thioanisole, characterized in that: The steps include: In the first step, thioanisole, tert-butyl alcohol and ethyl acetate are added into the reaction bottle in sequence; The second step is to adjust the pressure reducing valve of the oxygen cylinder and set the partial pressure to 0.1 MPa. After the oxygen enters the ozone generator, an ozone mixed gas is generated. The gas flow rate is set to 100 L / h. The ozone mixed gas enters the reaction bottle to react with the reactants. The gas phase concentration of ozone is controlled to be 20-100 mg / L. The third step is to introduce the ozone mixed gas into the reaction bottle, and set the reaction liquid temperature to 25°C and the reaction time to 30-60 minutes; The fourth step is to remove the reaction solvent by distillation under reduced pressure after the reaction is completed, and then separate the product benzyl sulfoxide by column chromatography.

2. The method for synthesizing benzyl sulfoxide by selective oxidation of thioanisole according to claim 1, wherein: The dosage of thioanisole in the first step is 1-5 mL.

3. The method for synthesizing benzyl sulfoxide by selective oxidation of thioanisole according to claim 1, characterized in that: The amount of tert-butyl alcohol used in the first step is 100-500 mg.

4. The method for synthesizing benzyl sulfoxide by selective oxidation of thioanisole according to claim 1, characterized in that: The volume ratio of thioanisole to ethyl acetate in the first step is 1:50 to 1:100.

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